We propose development of an advanced functional imager to assess red blood cell (RBC) transfusion. The prototype will be tested in a functional phantom during this SBIR Phase I project. The key features of the imager are the ability to quantify local tissue oxygenation with a handheld probe for easy tissue access. Our preliminarily market research indicates a strong demand for such instrument to help physicians effectively perform RBC transfusion, which is the most common inpatient hospital procedure. We hypothesize that non-invasive technology capable of providing repeated 3-D functional maps of tissue microvessels with diameters between 20-50 m, where oxygen starts diffusing to the parenchymal tissues, will significantly decrease morbidity and mortality in RBC transfusion. Such technology has the potential to guide procedures by providing favorable information about optimal transfusion threshold, as well as evaluation of RBCs degradation with storage time and conditions. Current imaging technologies used to assess RBC transfusion include: Sidestream Dark Field (SDF), Orthogonal Polarization Spectral (OPS) and Near Infrared Spectroscopy (NIRS) do not provide 3-D maps of microvascular blood oxygenation and flow in a single microvessel with diameter 20-50 m. SDF and OPS provide 2-D non-depth-resolved angiography and blood flow microvasculature information, thus missing the oxygenation information and arterioles and venules discrimination. The NIRS provides average arterial oxygenation information from a few square mm area and thus misses oxygen extraction, blood flow and spatial resolution. We propose to fill this gap with the proposed imaging technology for RBC transfusion assessment by combining multifunctional optical coherence tomography (OCT) and OPS in a single hand- held device. OPS offers real-time 2-D microvasculature map for user guidance purposes while multifunctional OCT provides 3-D microvasculature angiography and maps of blood flow and hemoglobin oxygen (O2) saturation (SO2) in single arterioles and venules as well as O2 extraction and relative oxygen consumption. We believe our approach provides the needed performance to solve a critical problem and a clear path to successful commercialization. This project will have strong social impact by providing critical clinical information to improve patient outcomes. Quantitative imaging of local tissue oxygen delivery and consumption will not only improve RBC transfusion outcome but has a great potential to decrease morbidity and mortality in many devastating diseases with vascular etiology including a variety of malignant, inflammatory, ischemic, infectious and immune disorders.